The main purpose of this proposal is to develop a novel interface for on- line coupling of liquid separation techniques to a mass spectrometer (MS) using an atmospheric pressure (AP) infrared (IR) matrix-assisted laser desorption/ionization (MALDI) method. In contrast to conventional MALDI where ions are formed inside a vacuum system. In AP MALDI they are produced at normal atmospheric pressure. AP MALDI was first demonstrated and later commercialized using an ultraviolet (UV) laser. It showed sensitivity comparable to that of conventional MALDI, a large tolerance to the laser energy, and minimal fragmentation of analyte ions. AP MALDI interfaced with an ion trap mas spectrometer brings unique capability off tandem MS (or MS/MS) to MALDI analysis. Since AP UV-MALDI uses mostly solid organic matrices it like conventional UV- MALDI usually allows off-line analysis only. The use of an IR laser will allow one to use significantly larger number of matrices for MS analysis including liquid ones. Given excellent absorption or organic compounds in the IR spectral range the AP IR-MALDI makes possible direct coupling of liquid separation techniques =to MS, thus, the perspective of having both MALDI and electrospray ion sources for liquid analysis on the same mass analyzer becomes very feasible. PROPOSED COMMERCIAL APPLICATIONS: Atmospheric Pressure IR-MALDI for interfacing mass spectrometers to liquid separation techniques as well as for off-line analysis. This method has many biological and biomedical applications in research labs, hospitals, industry, and defense where analysis of proteins, peptides, DNA & RNA is utilized. Commercialization of the method by SESI is straightforward.